Caveolins and intracellular calcium regulation in human airway smooth muscle

Y. S. Prakash, Michael A. Thompson, Brianna Vaa, Ihaab Matabdin, Timothy E. Peterson, Tongrong He, Christina M. Pabelick

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Regulation of intracellular Ca2+ concentration ([Ca 2+]i) is a key factor in airway smooth muscle (ASM) tone. In vascular smooth muscle, specialized membrane microdomains (caveolae) expressing the scaffolding protein caveolin-1 are thought to facilitate cellular signal transduction. In human ASM cells, we tested the hypothesis that caveolae mediate Ca2+ responses to agonist stimulation. Fluorescence immunocytochemistry with confocal microscopy, as well as Western blot analysis, was used to determine that agonist receptors (M3 muscarinic, bradykinin, and histamine) and store-operated Ca2+ entry (SOCE)-regulatory mechanisms colocalize with caveolin-1. Although caveolin-2 coexpressed with caveolin-1, caveolin-3 was absent. In fura 2-loaded ASM cells, [Ca2+]i responses to 1 μM ACh, 10 μM histamine, and 10 nM bradykinin, as well as SOCE, were attenuated (each to a different extent) after disruption of caveolae by the cholesterol-chelating drug methyl-β-cyclodextrin. Transfection of ASM cells with 50 nM caveolin-1 small interfering RNA significantly weakened caveolin-1 expression and blunted [Ca2+]i responses to bradykinin and histamine, as well as SOCE, but the response to ACh was less intense. These results indicate that caveolae are present in ASM and that caveolin-1 contributes to regulation of [Ca2+]i responses to agonist.

Original languageEnglish (US)
Pages (from-to)L1118-L1126
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number5
DOIs
StatePublished - Nov 1 2007

Keywords

  • Intracellular signaling pathway
  • Methyl-β-cyclodextrin
  • RNA
  • Small interfering
  • Store-operated calcium entry

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Caveolins and intracellular calcium regulation in human airway smooth muscle'. Together they form a unique fingerprint.

  • Cite this